Establishment of the DNAJB8 targeting dendritic cell immunotherapy induced from iPS cells

• Project/Area Number: 17K16811
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Wakayama Medical University
• Principal Investigator: NISHIZAWA SATOSHI 和歌山県立医科大学, 医学部, 助教 (90458076)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: DNAJB8 / Dnajb8 / iPS細胞 / 樹状細胞 / 癌幹細胞 / 免疫療法 / 癌免疫療法

Outline of Final Research Achievements

Sox2, Oct3/4, Klf4, and L-myc were introduced into Balb/c mouse-derived fibroblast cell line balb/3T3 using Sendai virus vector to induce iPS cells. We tried to induce dendritic cells from induced iPS cells, but we could not confirm the expression of CD11b, MHC class II, and CD80/86 by FACS. To examine the clinical role of DNAJB8, mRNA was extracted from tissue samples of 52 renal cancer patients who underwent radical nephrectomy in our hospital, and its association with clinical prognosis was evaluated by quantitative PCR. No recurrence was observed in 14 cases with no expression of DNAJB8, and pathologically, there was a significant difference in venous invasion depending on the expression of DNAJB8.

Academic Significance and Societal Importance of the Research Achievements

当研究においてDNAJB8を標的とした免疫療法の確立のため、iPS細胞から誘導した樹状細胞を用いてその癌抑制効果を評価する予定であったが、樹状細胞の誘導が困難で断念せざるを得なかった。当研究と並行してDNAJB8の臨床的意義についても評価を行ったが、DNAJB8は根治治療後の癌再発とも臨床的に相関し、癌起始能を有すると考えられる癌幹細胞との関連を臨床的にも確認でき、DNAJB8を標的とした治療戦略の有用性を再評価できたと考えられる。

Research Products

• [Journal Article] Identification of antigenic peptides from novel renal cancer stem-like cell antigen, DNAJB8 (2017)
  • Author(s): Nishizawa S, Hirohashi Y, Kusumoto H, Wakamiya T, Iguchi T, Yamashita S, Iba A, Kikkawa K, Kohjimoto Y, Torigoe T, Hara I
  • Journal Title: Biochem Biophys Res Commun Volume: 494 Issue: 3-4 Pages: 693-699
  • DOI: 10.1016/j.bbrc.2017.10.146
  • Peer Reviewed